Esposito Irene, Seiler Christopher, Bergmann Frank, Kleeff Jörg, Friess Helmut, Schirmacher Peter
Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
Pancreas. 2007 Oct;35(3):212-7. doi: 10.1097/mpa.0b013e31805d0190.
Based mainly on animal models, 2 lesions have been suggested as possible precursors of pancreatic ductal adenocarcinoma (PDAC): pancreatic intraepithelial neoplasia (PanIN) and tubular complexes (TCs). The aim of the study was to find support for either of the 2 models through the analysis of a large panel of human pancreatic tissues.
Ninety-two PDAC, 45 chronic pancreatitis, and 27 serous cystadenoma cases were investigated using conventional morphology and immunohistochemistry.
Most of the cases (78% of PDAC, 93% of chronic pancreatitis, and 67% of serous cystadenoma) exhibited putative precursor lesions, predominantly TC and low-grade PanIN lesions, often present in the same tissue area. High-grade lesions were exclusively observed in PDAC specimens. In 50% to 70% of the cases with TC and associated PanIN, a transitional zone of acinar-ductular transformation with mucinous differentiation of the ductular epithelium was identified. Expression of acinar and centroacinar markers was detected in TC, in the ductular structures of the transitional zones, as well as within the epithelium of mature PanINs.
The results of the present study show that the coexistence of 2 different putative PDAC precursor lesions might not be a contradiction. A progression model that originates in the centroacinar-acinar compartment and ends with the development of PanIN lesions is suggested.
主要基于动物模型，已提出两种病变可能是胰腺导管腺癌（PDAC）的前体病变：胰腺上皮内瘤变（PanIN）和管状复合体（TC）。本研究的目的是通过分析大量人类胰腺组织来寻找对这两种模型中任一种的支持依据。
采用传统形态学和免疫组织化学方法对92例PDAC、45例慢性胰腺炎和27例浆液性囊腺瘤病例进行研究。
大多数病例（78%的PDAC、93%的慢性胰腺炎和67%的浆液性囊腺瘤）表现出假定的前体病变，主要为TC和低级别PanIN病变，且常出现在同一组织区域。高级别病变仅在PDAC标本中观察到。在50%至70%伴有TC及相关PanIN的病例中，发现了腺泡-导管化生的过渡区，其导管上皮有黏液样分化。在TC、过渡区的导管结构以及成熟PanIN的上皮内均检测到腺泡和中央腺泡标志物的表达。
本研究结果表明，两种不同的假定PDAC前体病变共存可能并非矛盾现象。提出了一种起源于中央腺泡-腺泡区室并以PanIN病变发展告终的进展模型。
